Treatments of disorders using nucleic acid drugs include antisense therapies, antigene therapies, aptamers, siRNAs and the like. An antisense therapy is the procedure for treatment or prevention of diseases involving inhibiting a translation process of pathogenic RNAs by externally introducing disease-associated mRNAs and their complementary oligonucleotides (antisense strands) to form the double strands. SiRNAs have the similar mechanism as the antisense therapies, involving inhibiting translation from mRNAs to proteins by administration of double-stranded RNAs to the body. Meanwhile, in the antigene therapies, transcription of DNA to RNA is inhibited by externally introducing triple-strand-forming oligonucleotides corresponding to the DNA sites transcribed into the pathogenic RNA. Aptamers, which are small nucleic acid molecules (oligonucleotides), exert their functions by binding to disease-related biological components, such as proteins.
Although various artificial nucleic acids has been developed as materials for such nucleic acid drugs, there has not been found ideal molecules yet. For example, the materials developed for nucleic acid drugs to date include S-oligo (phosphorothioate), 2′,4′-BNA (bridged nucleic acid)/LNA (locked nucleic acid) (See Patent Documents 1 to 3 and Non-patent Documents 1 to 4). S-oligo is commercially available as an antisense drug for cytomegalovirus in United States. While this drug has a high nuclease resistance, it has a problem to be improved concerning about its low binding affinity to the target nucleic acid strands. Every 2′,4′-BNA/LNAs which have ever been developed have high binding affinities to their target nucleic acid strands and they are the most promising molecules as the materials for the future nucleic acid drugs. However, they still remain to be improved with regard to their nuclease resistance which is not enough to be stable in vivo.